Cobalt-Catalyzed Amide Bond Formation from Esters and Amines.

Abstract

Amide bonds are ubiquitously present in natural products and drug molecules. Traditional methods for constructing amide bonds rely on stoichiometric activating reagents, often leading to the generation of substantial waste. Therefore, the development of green and sustainable synthetic approaches is of significant importance. This study reports a novel cobalt complex catalyst prepared by using inexpensive and readily available CoCl2 as a precursor, which efficiently promotes the amidation of esters with amines. Under optimized reaction conditions (toluene as the solvent, 15 mol % sodium tert-butoxide as the base, 0.6 mol % cobalt complex Cat-1 as the catalyst, 120 °C under a nitrogen atmosphere), the catalytic system exhibits high compatibility with various substituted methyl benzoates, heterocyclic esters, aromatic amines, and secondary amines, delivering products in 40%-85% yields. Notably, it also demonstrates minimal racemization toward chiral substrates with ee values maintained 85-99%. Furthermore, the method has been successfully applied to the synthesis of plant oil-based amide compounds and gram-scale reactions, highlighting its practical utility. This research provides an efficient and atom-economical new strategy for the green synthesis of amide bonds.